TMSOTf-Catalyzed Acylation of Alcohols with Acid Anhydrides
J . Org. Chem., Vol. 63, No. 7, 1998 2347
a ceta te (11): 1H NMR (CDCl3) δ 0.84, 1.23, 1.38, 1.44, 2.14
and 2.16 (6s, 3H each), 4.73 (d, J ) 18 Hz, 1H), 4.97 (d, J )
18 Hz, 1H), 5.01 (d, J ) 5 Hz, 1H), 5.25 and 5.45 (2m, 1H),
5.49 (m, 1H), 6.39 (dd, J ) 10 and 2 Hz, 1H), 6.45 (s, 1H),
6.79 (d, J ) 10 Hz, 1H); TSMS m/z 537 (M + H)+. Anal. Calcd
for C28H34F2O8 C, 62.68; H, 6.39. Found: C, 62.86; H, 6.34%.
11â-(Acetyloxy)-6r,9r-diflu or o-21-h ydr oxy-16r,17r-(iso-
p r op ylid en ed ioxy)-3,20-d ioxop r egn a n e-1,4-d ien e-21-yl
6.79 (d, J ) 10 Hz, 1H); TSMS m/z 511 (M + H)+. Anal. Calcd
for C26H32F2O6S C, 61.16; H, 6.32; S, 6.28. Found: C, 60.99;
H, 6.33; S, 6.23%.
6r,9r-Diflu or o-16r-m et h yl-3-oxo-11â,17r-b is(p r op io-
n yloxy)-a n d r osta -1,4-d ien e-17â-ca r boxylic Acid (23). A
mixture of the carboxylic acid45 22 (192 mg, 0.5 mmol) in CH2-
Cl2 (2 mL) and propionic anhydride (0.57 mL, 4.5 mmol) was
treated at 20 °C with a solution of TMSOTf in CH2Cl2 (1 M;
20 µL), and the mixture was stirred for 2 h. The reaction
mixture was diluted with CH2Cl2 and treated with aqueous
concentrated ammonia for 5 min. The two phases were
separated, and the organic solution was retreated with am-
monia. TLC indicated removal of the less polar product and
the formation of a polar product. The organic layer was
washed with 2 M HCl, dried, and evaporated to a white solid
(140 mg, 55%): 1H NMR (CDCl3) δ 0.94 (d, J ) 7 Hz, 3H),
1.00 (s, 3H), 1.12 (t, J ) 7 Hz, 6H), 1.37 (s, 3H), 3.32 (m, 1H),
5.26 and 5.45 (2m, 1H), 5.47 (m, 1H), 6.38 (dd, J ) 10 and 2
Hz, 1H), 6.44 (s, 1H), 6.80 (d, J ) 10 Hz, 1H); TSMS m/z 509
(M + H)+. Anal. Calcd for C27H34F2O7‚1.75H2O: C, 60.05; H,
7.00. Found: C, 60.12; H, 6.96%.
Effect of Solven t in th e Acetyla tion of Mesyla te 13a .
Twelve reactions were set up using alcohol 13a (160 mg, 0.3
mmol) in a solvent (5 mL), acetic anhydride (0.1 mL, 1.06
mmol), and TMSOTf in CH2Cl2 (1 M; 30 µL, 0.1 equiv), and
the mixtures were stirred at 20 °C for 3 h. Aliquots were taken
out, diluted in CH3CN (150 µL) and MeOH (50 µL), and
examined by HPLC. The results are shown in Table 2.
Acetyla tion of 2-(4-h yd r oxyp h en yl)eth a n ol (35) u sin g
a s follow s:
(a ) Ac2O a n d DMAP . 2-(4-Hydroxyphenyl)ethanol (35)
(1.38 g, 10 mmol) and Ac2O (0.95 mL, 10 mmol) in CH2Cl2 (30
mL) were treated with Et3N (2 mL, 10 mmol) and DMAP (122
mg, 1 mmol) at 20 °C, and the mixture was stirred for 4 d.
Analytical HPLC indicated a mixture tR ) 5.531 min 53.5%,
6.626 min 13.3%, and 8.670 min 33.2%. The mixture was
diluted with CH2Cl2 and washed with 2 M HCl, NaHCO3, H2O,
dried, and chromatographed on silica gel eluting with ethyl
acetate-cyclohexane (1:3, 1:1) to give the diacetate21,23 (38)
(500 mg, 22%) tR ) 8.664 min: 1H NMR (CDCl3) δ 2.05 (s,
3H), 2.30 (s, 3H), 2.94 (t, J ) 7 Hz, 2H), 4.28 (t, J ) 7 Hz, 2H),
7.02 (d, J ) 8 Hz, 2H), 7.24 (d, J ) 8 Hz, 2H); ESMS m/z 240
(M + NH4)+
m eth a n esu lfon a te (13b): IR (KBr) 1749, 1731, 1671 cm-1
;
1H NMR (CDCl3) δ 0.79, (s, 3H), 1.13 (s, 3H), 1.38 (s, 6H), 2.10
(s, 3H), 3.28 (s, 3H), 4.91 (m, 1H), 4.99 (d, J ) 18 Hz, 1H),
5.27 (m, 1H), 5.35 (d, J ) 18 Hz, 1H), 5.53 and 5.72 (2m, 1H),
6.14 (s, 1H), 6.35 (dd, J ) 10 and 2 Hz, 1H), 6.83 (d, J ) 10
Hz, 1H), 5.77 (CH2Cl2); TSMS m/z 573 (M + H)+. Anal. Calcd
for C27H34F2O9S.0.33CH2Cl2 C, 54.65; H, 5.82; S, 5.34.
Found: C, 54.53; H, 5.80; S, 5.25%.
11â-(Acetyloxy)-6r,9r-d iflu or o-17r-h yd r oxy-16r-m eth -
yl-3-oxoa n d r osta -1,4-d ien e-17â-ca r both ioic Acid , Meth yl
Ester (20). A solution of diol45 19 (213 mg, 0.5 mmol) in CH2-
Cl2 (2 mL), triethylamine (1.5 mL, 10.76 mmol), and Ac2O (0.6
mL, 6.3 mmol) was treated with DMAP (9.1 mg, 0.075 mmol),
and the mixture was stirred at 20 °C for 7 h. The reaction
mixture was diluted with EtOAc, and 2 M HCl was added.
The organic phase was washed with 2 M HCl, NaHCO3, and
brine, dried, and evaporated to dryness. The residue was
recrystallized twice from MeOH to give 20 (49 mg, 21%) as
white crystals: IR (KBr) 3484, 1744, 1731, 1681, 1667 cm-1
;
1H NMR (CDCl3) δ 0.96 (s and d, J ) 7 Hz, 6H), 1.37 (s, 3H),
2.10 (s, 3H), 2.27 (s, 3H), 3.0-3.2 (m, 1H), 5.24 (m, 0.5 H),
5.37-5.49 (m, 1.5H), 6.37 (dd, J ) 10 and 2 Hz, 1H), 6.42 (s,
1H), 6.75 (dd, J ) 10 and 1 Hz, 1H); ESMS m/z 469 (M + H)+
(30%), 936 (2M + H)+ (100%). Anal. Calcd for C24H30F2O5S
C, 61.52; H, 6.45; S, 6.84. Found: C, 61.54; H, 6.66; S, 6.70%.
11â,17r-(Dia ce t yloxy)-6r,9r-d iflu or o-16r-m e t h yl-3-
oxoa n d r osta -1,4-d ien e-17â-ca r both ioic a cid , m eth yl es-
1
ter (21): IR (KBr) 1746, 1672 cm-1; H NMR (CDCl3) δ 0.94
(s, 3H), 1.02 (d, J ) 7 Hz, 3H), 1.37 (s, 3H), 2.07 (s, 3H), 2.11
(s, 3H), 2.35 (s, 3H), 3.3-3.5 (m, 1H), 5.24 (m, 0.5H), 5.4-
5.52 (m, 1.5 H), 6.38 (dd, J ) 10 and 1 Hz, 1H), 6.45 (s, 1H),
(29) Posner, G. H.; Okada, S. S.; Babiak, K. A.; Miura, K.; Rose, R.
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5607.
the O-aryl acetate21 (36) (705 mg, 39%), tR ) 5.585 min: 1H
NMR (CDCl3) δ 1.85 (br s, 1H), 2.29 (s, 3H), 2.83 (t, J ) 7 Hz,
2H), 3.80 (t, J ) 7 Hz, 2H), 7.01 (d, J ) 8 Hz, 2H), 7.22 (d, J
) 8 Hz, 2H); ESMS m/z 198 (M + NH4)+ and the O-alkyl
acetate22,23 (37) (54 mg, 3%), tR ) 6.547 min: 1H NMR (CDCl3)
δ 2.04 (s, 3H), 2.85 (t, J ) 7 Hz, 2H), 4.23 (t, J ) 7 Hz, 2H),
6.22 (s, 1H), 6.75 (d, J ) 8 Hz, 2H), 7.05 (d, J ) 8 Hz, 2H);
ESMS m/z 198 (M + NH4)+
(b) TMSOTf. 2-(4-Hydroxyphenyl)ethanol (35) (1.38 g, 10
mmol) in CH2Cl2 (10 mL) and Ac2O (0.95 mL, 10 mmol) was
treated with TMSOTf in CH2Cl2 (1 M; 0.25 mL) at 20 °C. The
reaction mixture was checked by HPLC after 1 h and indicated
a mixture (22:48:30). After stirring for 21 h, the starting
material was consumed and the mixture of products was 88:
12. After stirring for a total of 3.5 d the ratio improved to
93:7. The mixture was washed with water and brine, dried,
and evaporated to give 37 (1.577 g, 88%): 1H NMR (CDCl3) δ
2.05 (s, 3H), 2.85 (t, J ) 7 Hz, 2H), 4.24 (t, J ) 7 Hz, 2H), 5.92
(s, 1H), 6.77 (d, J ) 8 Hz, 2H), 7.07 (d, J ) 8 Hz, 2H).
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masthead page for ordering information.
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